The present proposal concerns central nervous system (CNS) infection with herpes simplex virus type 1 (HSV). Mice are inoculated with HSV by corneal scarification (trigeminal model) and by injection into the muscle of the tongue (hypoglossal model). The course of the infection is followed by histopathology, immunohistopathology, and infectivity assays. A latent infection in brain stem is confirmed by the explantation technique (in vitro reactivation). The immunoperoxidase technique is used to determine the cell type in the CNS in which viral antigens first appear after in vitro reactivation. To reactivate HSV in vivo mice are treated with immunosupressive agents and with neurectomy in the hypoglossal model. Reactivation trials are monitored closely to determine if HSV replication resumes in the CNS or if some viral antigens appear without HSV replication. Either mechanism may produce tissue damage: the first by direct viral destruction and the second by an immune-mediated mechanism.